脾加骨髓细胞移植治疗小鼠大肠癌的实验研究

Experiment Research on the Spleen and Bone Marrow Cell Transplantation in the treatment of Colorectal Cancer in Mice

目的:探讨半相合脾加骨髓细胞移植治疗小鼠大肠癌的效果及其对嵌合体水平和移植物抗宿主病(GVHD)的影响。方法:以接种CT26大肠癌细胞的BALB/c×C57BL/6杂交Fl代雌性小鼠为受鼠,以健康雌性Fl、雄性C57BL/6、雄性C3H小鼠为MHC全相合、半相合、不相合供鼠,观察移植后的抑瘤情况;另设5只化疗联合半相合脾加骨髓细胞移植的小鼠为监测组,用来作嵌合体的分析,观察各组GVHD的情况。结果:经化疗预处理的脾加骨髓细胞移植组小鼠肿瘤明显缩小,与单纯化疗未进行移植组比较,差异具有统计学意义(P<0.05);化疗联合半相合脾加骨髓细胞移植的小鼠于移植3周后达完全供者植入,于移植后第10天左右出现纳差、倦怠、步态不稳、脱毛、腹泻、体重明显下降等GVHD的症状。结论:化疗预处理联合脾加骨髓细胞移植能对CT26大肠癌细胞产生GVT效应,并伴随着GVHD及嵌合率的变化。

Objective： To investigate the anti-tumor effects and the effect condition of the chimera level and GVHD of transplanting MHC half-matched bone marrow cells combined with spleen cells in a murine model bearing colorectal cancer. Methods： Female （BALB/exC57BI/6）FI mice （CB6FI, H-2Kb/d） were subcutaneously inoculated with CT26 cells to develop a solid tumor model. The syngenic, half-matched, and mismached donor bone marrow cells were from healthy female FI, maleC57BL/6 （H-2Kb）, and male C3H （H-2K）mice, respectively. The tumor weights were measured after transplantation. Meanwhile, the testing-group which received chemotherapy, transplanting MHC half-matched bone marrow cells combined with spleen cells was used to analyze the chimera level. And GVHD were observed after the transplantation. Results： The tumor weights of mice undergone chemotherapy pretreatment, bone marrow cells combined with spleen cells were significantly decreased compared with those of the mice receiving chemotherapy alone （P 〈0.05）. The mice which received chemotherapy, transplanting MHC half-matched bone marrow cells combined with spleen cells attained donor implanted completely in 3 weeks after transplantation. Then began to fall ill at 10 days post-transplantation, GVHD symptoms including decreased appetite, tired,instability of gait, unhairing, lose weight, diarrhea. Conclusion： Transplantation of chemotherapy preprocess, MHC bone marrow cells combined with spleen cells could induce GVT effect in mice bearing CT26 tumor, which accompanied with the change of GVHD and ehimerism.